Topic: SUMOylation

Cellular hallmarks of neurodegenerative diseases include loss of synapses, neuronal death, inflammation, energy homeostasis defects, oxidative stress, mitochondrial dysfunction, and aberrant proteostasis. AMP-activated kinase (AMPK) maintains energy homeostasis by responding to fluctuating ATP levels, with diverse targets ranging from changing the transcriptional program, promoting glucose uptake, inhibiting protein synthesis, inducing mitochondrial fission, mitophagy and autophagy. Evidence indicates that AMPK is hyperactivated in Alzheimer’s disease (AD), and amyloid-β (Aβ) can activate AMPK

The Angelman Syndrome (AS) is a rare neurodevelopmental disorder caused by the loss of the maternally expressed UBE3A gene, which encodes an E3 ubiquitin ligase. Although considerable efforts have been put to dissect UBE3A function in the brain, the pathogenic mechanisms remain largely unknown and effective treatments are not available yet. Being an E3 ubiquitin ligase, defective ubiquitination, which may occur in either nuclear or cytosolic compartments, is thought to be a primary mechanism underlying synaptic dysfunction in AS. Increasing evidence indicates a tight functional interplay betwe

SUMOylation is a covalent and reversible attachment of an 11 kDa SUMO (Small Ubiquitin-like MOdifier) protein to a lysine residue. SUMOylation act as a biochemical switch to regulate the function of hundreds of proteins in different pathways. In the brain of vertebrates, three main SUMO isoforms (SUMO1-3) are characterized. While SUMO2 and SUMO3 differ by only three N-terminal amino acids, they only share ~50% of their sequences with SUMO1. Global levels of SUMOylated proteins are altered in several neurodegenerative diseases; however, no data are currently available in Fronto-temporal dementi

Ophn1 gene encodes Oligophrenin-1 (OPHN1), a Rho-GAP protein highly expressed in neurons. In humans, all Ophn1 mutations cause the loss of function of OPHN1 leading to syndromic intellectual disability (ID). In neurons, OPHN1 regulates dendritic spine density and architecture, actin dynamics and AMPA receptor (AMPAR) trafficking. Interestingly, we identified for the first time OPHN1 as a novel target of sumoylation. Sumoylation is a post-translational modification essential to the modulation of several neuronal functions, including neurotransmitter release and synaptic plasticity. Altered sumo